Hypertension is one of the most prevalent diseases worldwide. Increased synthesis of the vasoconstrictor peptide endothelin 1 (encoded by EDN1) might be responsible for high blood pressure. The present study further confirmed the abnormal EDN1 upregulation within adipose tissue-derived stromal cells (ADSCs) derived from morbidly obese subjects. The overexpression of EDN1 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by human umbilical vein endothelial cell (HUVEC). Transcription factor NR4A3 was positively correlated with EDN1, binding to EDN1 promoter region to upregulate EDN1 expression. Similarly, the overexpression of NR4A3 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by HUVECs, as well as EDN1 protein levels in ADSCs. However, the effects of NR4A3 overexpression on EDN1 protein levels in ADSCs and the proliferation and migration of HUVECs and tube formation by HUVECs were significantly reversed by EDN1 silencing in ADSCs. In conclusion, NR4A3 is abnormally upregulated in ADSCs derived from morbidly obese subjects; NR4A3 could promote HUVEC angiogenesis through binding to EDN1 promoter and upregulating EDN1 expression.

高血压是全世界最普遍的疾病之一。血管收缩肽内皮素1（由EDN1编码）合成增加可能是高血压的原因。本研究进一步证实了来自病态肥胖受试者的源自脂肪组织的基质细胞（ADSC）中的异常EDN1上调。EDN1在非肥胖受试者来源的ADSC中的过表达显着促进了人脐静脉内皮细胞（HUVEC）的HUVEC增殖和迁移以及管形成。转录因子NR4A3与EDN1正相关，与EDN1启动子区域结合以上调EDN1表达。同样，在非肥胖受试者的ADSC中NR4A3的过表达显着促进了HUVEC的增殖和迁移以及HUVEC形成的管，以及ADSC中的EDN1蛋白水平。然而，NR4A3过表达对ADSCs中EDN1蛋白水平以及HUVECs的增殖和迁移以及HUVECs管形成的影响被ADSCs中的EDN1沉默显着逆转。总之，NR4A3在源自病态肥胖受试者的ADSC中异常上调。NR4A3可以通过与EDN1启动子结合并上调EDN1表达来促进HUVEC血管生成。